P1493: CHRONIC COMPLICATIONS IN THE EAST LONDON SICKLE NEWBORN COHORT STUDY (ELSNCS)
Authors: C. Sangarappillai, M. Soriano, J. Bestwick, D. Kafuko, K. Newell, B. Kaya, S. Bennett, F. Barroso, D. Tsitsikas, P. Telfer
Journal: HemaSphere (2022)

Background: Current standard of care for sickle cell disease (SCD) has resulted in a significant reduction in childhood mortality. It is likely that health is improved also for adults, but the expected residual chronic morbidity and reduced life expectancy is not clear, and accurate prognosis is important for planning health care services and in evaluating the impact of new therapies. The ELSNCS has been recruiting consecutive infants diagnosed within a universal newborn screening programme since 1983. Subjects have been managed in a relatively seamless paediatric and adult specialised service in the UK National Health Service during the era where standard of care has evolved. Aims: This study provides an opportunity to make an early estimate of the risk of recognised chronic morbidities. Methods: Eligible patients were born in the London Boroughs of Hackney and Tower Hamlets, diagnosed by newborn screening, with initial referral to Royal London Hospital (RLH) Paediatric Sickle Cell Service and seen at least once. Permission to study all patients without individual consent was obtained from the UK National Confidentiality Advisory Group and National Research Ethics Committee. All clinical data on these patients has been captured in a designated clinical and research database maintained in our service over the past 22 years. A set of definitions for each complication was developed based on published literature and consensus group discussion taking into account the nature of the cohort data. For each subject, clinical data was validated against source records up to death, stem cell transplant, or follow-up cut set at December 31,2018. Risks of developing specific complications (95%CI) were estimated at age 25 by Kaplan Meier survival analysis. Results: There were 404 subjects (268 HbSS, 118 HbSC, 17 HbS beta thal, 1 HbS beta 0). 200 were female. At time of data cut, mean age was 13.3 years (age range 0.3 – 35.4),11 had died, 6 had BMT. 172 (42.6%) were under follow-up in paediatrics at RLH, 93 (23.0%) in adult at RLH, 95 (23.5%) had transferred care to another clinic, 12 (3.0%) were known to be alive but not under follow-up and 15 (3.7%) had been lost to follow-up. During follow-up 93 (23.0%) had been treated with chronic transfusion for more than 6 months and 95 (23.5%) with Hydroxyurea for more than 6 months Risks of chronic complications at age 25 are shown in the table. Image:Summary/Conclusion: Estimated survival for HbSS at age 25 is 92.1%, and there is an increase in mortality in adolescents and young adults as reported in other cohorts. Most mortality is due to acute complications and all genotypes are affected. The ELSNCS provides unique data to inform an unbiased estimate of risks for chronic complications of SCD in the context of current standard of care. Although not sufficiently mature to estimate risks of SCD-related severe heart, kidney and liver failure, there is already significant morbidity associated with pulmonary hypertension, cerebrovascular disease, and avascular necrosis in the HbSS genotype despite standard therapy, and this suggests the need to intensify current treatment, and consider new therapeutic options which might mitigate the risk of chronic complications.